牛乳・乳製品

参考文献

1. 参考図書

   Fukagawa NK, McKillop K, Pehrsson PR, Moshfegh A, Harnly J, Finley J. USDA's FoodData Central: what is it and why is it needed today? American Journal of Clinical Nutrition, 2022.

   doi:10.1093/ajcn/nqab397PubMed 34893796

   資金と結果

   資金提供

   All authors are employed by the USDA Agricultural Research Service and have not received external support in the preparation of this manuscript.

   結果

   FoodData Central Foundation Foods, per 100 g. Milk, whole, 3.25% milkfat, with added vitamin D (FDC 746782): water 88.1 g, lactose 4.81 g, protein 3.27 g, total fat 3.2 g, calcium 123 mg, energy 60 kcal (Atwater specific factors); saturated fatty acids 1.86 g, including 15:0 0.032 g and 17:0 0.018 g; trans 16:1 0.008 g, trans 18:1 0.082 g; 1 cup 249 g. Cheese, cheddar (FDC 328637): protein 23.3 g, total fat 34.0 g, calcium 707 mg, lactose 0.16 g.

2. 参考図書

   UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025 Nucleic Acids Research, 2025.

   doi:10.1093/nar/gkae1010PubMed 39552041

   資金と結果

   資金提供

   National Human Genome Research Institute (NHGRI) [HG002273]; Office of the Director, NIH OD [U24HG007822]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA); National Institute of General Medical Sciences (NIGMS) [R35GM141873]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Eye Institute (NEI); National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); Biotechnology and Biological Sciences Research Council (BBSRC) [BB/T015608/1]; National Science Foundation's Directorate for Biological Sciences [BB/X002179/1]; Open Targets; Horizon 2020 - Research and Innovation Framework Programme [825575]; State Secretariat for Education, Research and Innovation (SERI); European Molecular Biology Laboratory (EMBL) Australia. Funding for open access charge: National Institutes of Health.

   結果

   Reviewed human entries read 2026-10-21. PNLIP (P16233) preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids. CLPS (P04118) is a cofactor that anchors pancreatic lipase at the lipid-water interface; without it bile salts wash the enzyme off. MOGAT2 (Q3SYC2) transfers an acyl chain from acyl-CoA to monoacylglycerol, forming diacylglycerol. DGAT1 (O75907) catalyses the terminal and only committed step of triacylglycerol synthesis, is highly expressed in small-intestinal epithelial cells and is essential for absorption of dietary fats. MTTP (P55157) transports triglyceride, cholesteryl ester and phospholipid between phospholipid surfaces and is required for assembly and secretion of apolipoprotein B-containing lipoproteins. APOB (P04114): apo B-48 is a major protein of chylomicrons. SCD (O00767) inserts a cis double bond at the delta-9 position of fatty acyl-CoA substrates including stearoyl-CoA, using O2 and electrons from reduced cytochrome b5. FDFT1 (P37268) condenses two farnesyl diphosphates to squalene, the first committed step of sterol biosynthesis. SQLE (Q14534) oxidises squalene to (S)-2,3-epoxysqualene and is considered rate-limiting in steroid biosynthesis. COMT (P21964) catalyses catechol + S-adenosyl-L-methionine = guaiacol + S-adenosyl-L-homocysteine; the Val158Met variant results in a 3- to 4-fold difference in activity. LCT (P09848), lactase/phlorizin hydrolase, a homodimer of the apical membrane of small-intestinal enterocytes, hydrolyses lactose to beta-D-galactose and D-glucose (EC 3.2.1.108). SLC5A1 (P13866, SGLT1) transports D-glucose or D-galactose across the apical membrane of enterocytes with 2 Na+ per sugar; basolateral exit is provided by GLUT2. SLC2A2 (P11168, GLUT2) is a facilitative transporter of glucose, fructose and galactose. GALM (Q96C23), GALK1 (P51570), GALT (P07902) and GALE (Q14376) constitute the Leloir pathway that converts beta-D-galactose to glucose 1-phosphate in the liver; GALM interconverts beta- and alpha-D-galactose, GALK1 phosphorylates alpha-D-galactose with ATP in the first committed step, GALT converts alpha-D-galactose 1-phosphate and UDP-glucose to alpha-D-glucose 1-phosphate and UDP-galactose, GALE interconverts UDP-glucose and UDP-galactose. PGM1 (P36871) isomerises alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate via glucose 1,6-bisphosphate. TRPV6 (Q9H1D0) is a calcium-selective channel that mediates Ca2+ uptake in tissues including the intestine. S100G (P29377) is calbindin-D9k, the intestinal vitamin D-dependent calcium-binding protein. ATP2B1 (P20020, PMCA1) transports calcium from the cytoplasm to the extracellular space, is located in the basolateral membrane and promotes intestinal calcium absorption.

3. 独立研究

   Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, et al. Convergent adaptation of human lactase persistence in Africa and Europe Nature Genetics, 2007.

   doi:10.1038/ng1946PubMed 17159977

   資金と結果

   参加者

   470

   資金提供

   L.S.B. Leakey and Wenner Gren Foundation grants; US National Science Foundation grants BSC-0196183, BSC-0552486 and IGERT-9987590; US National Institutes of Health grants R01GM076637, F32HG03801 and HG002772-1; David and Lucile Packard and Burroughs Wellcome Foundation Career Awards; Duke University Institute for Genome Sciences and Policy; Wellcome Trust.

   結果

   In most humans lactase-phlorizin hydrolase, which hydrolyses lactose into glucose and galactose in the small intestine, declines after weaning. Lactase persistence is inherited as a dominant trait in Europeans and its frequency exceeds 90% in Swedes and Danes, is about 50% in Spanish and French populations and about 1% in Chinese. C/T-13910 lies about 14 kb upstream of LCT within MCM6. Three African variants, G/C-14010, T/G-13915 and C/G-13907, arose on different haplotypes, are associated with lactase persistence and raise LCT promoter activity in vitro by about 18-30%; selection coefficients 0.04-0.097.

4. 独立研究

   Misselwitz B, Butter M, Verbeke K, Fox MR. Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management Gut, 2019.

   doi:10.1136/gutjnl-2019-318404PubMed 31427404

   資金と結果

   資金提供

   The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

   結果

   Narrative review, commissioned. In lactose malabsorption, colonic bacteria ferment lactose to hydrogen, carbon dioxide, methane and short-chain fatty acids; the osmotic load in the colon rises about eightfold. Lactase persistence in Europeans is mediated by LCT-13910 C>T within intron 13 of MCM6, 13.9 kb upstream of LCT. Cow's milk contains about 5 g lactose per 100 mL; yoghurt contains about 50% of the lactose of unprocessed milk, and cheese has low lactose content, especially long-ripened cheese. Lactose-free dairy products are made by adding lactase to milk.

5. 独立研究

   Liebert A, López S, Jones BL, Montalva N, Gerbault P, Lau W, et al. World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection Human Genetics, 2017.

   doi:10.1007/s00439-017-1847-yPubMed 29063188

   資金と結果

   資金提供

   EU Marie Curie ITN FP7 Framework Programme grant LeCHE (215362-2); Bicentennial Becas-Chile Scholarship, Chilean National Commission for Scientific and Technological Research (CONICYT); Annals of Human Genetics; MRC-DTA studentship.

   結果

   Lactase persistence is associated with at least five independent functional single nucleotide variants in a transcriptional enhancer about 14 kb upstream of LCT: -13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881). -13910*T has almost reached fixation in some parts of Europe; the others occur at variable frequencies in the Middle East and Africa.

6. 独立研究

   Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, et al. Calcium intake and risk of fracture: systematic review BMJ, 2015.

   doi:10.1136/bmj.h4580PubMed 26420387

   資金と結果

   資金提供

   Health Research Council of New Zealand. The authors are independent of the HRC, which had no role in study design, data collection, analysis, interpretation, writing or the decision to submit.

   結果

   Two randomised trials of dietary calcium sources reported fractures (262 participants); in the milk-powder trial (100 versus 100 women) there was 1 fracture versus 3 (RR 0.33, 95% CI 0.04 to 3.2). In cohort studies, 25 of 28 associations of milk intake and 11 of 13 of dairy intake with fracture were null. Calcium supplements: total fracture RR 0.89 (0.81 to 0.96; 20 trials), hip fracture 0.95 (0.76 to 1.18); no effect at any site in the 4 trials at lowest risk of bias.

7. 独立研究

   Michaëlsson K, Wolk A, Langenskiöld S, Basu S, Warensjö Lemming E, Melhus H, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies BMJ, 2014.

   doi:10.1136/bmj.g6015PubMed 25352269

   資金と結果

   参加者

   106,772

   追跡期間

   mean 20.1 years (women), 11.2 years (men)

   資金提供

   Grants from the Swedish Research Council. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit. One author is employed by the Swedish National Food Agency.

   結果

   Women, 3 or more glasses (600 g or more) of milk per day versus less than 1 glass: death 17.7 versus 10.7 per 1000 person-years (age standardised), adjusted HR 1.93 (95% CI 1.80 to 2.06); hip fracture 4.2 versus 3.1 per 1000 person-years, HR 1.60 (1.39 to 1.84); any fracture HR 1.16 (1.08 to 1.25). Per glass in women: mortality HR 1.15 (1.13 to 1.17), hip fracture 1.09 (1.05 to 1.13). Per glass in men: mortality 1.03 (1.01 to 1.04), any fracture 1.01 (0.99 to 1.03), hip fracture 1.03 (0.99 to 1.07). In women each serving of cheese or fermented milk was associated with 10-15% lower mortality and hip fracture rates. Milk intake was positively associated with urine 8-iso-PGF2alpha and, in men, serum interleukin 6. The authors proposed D-galactose, about 5 g per glass, as a mechanism on the basis of animal models of ageing and state that generalisation to humans needs further support; they recommend cautious interpretation because of possible residual confounding and reverse causation.

8. 独立研究

   Ding M, Li J, Qi L, Ellervik C, Zhang X, Manson JE, et al. Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies BMJ, 2019.

   doi:10.1136/bmj.l6204PubMed 31776125

   資金と結果

   参加者

   217,755

   追跡期間

   up to 32 years

   資金提供

   National Institutes of Health grants UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, R01 HL088521, UM1 CA176726, R01 CA67262, UM1 CA167552, R01 HL35464 and R01 HL60712. The funding sources did not participate in design, conduct, data collection, management, analysis, interpretation, or preparation, review or approval of the manuscript.

   結果

   51,438 deaths, including 12,143 cardiovascular. Highest (average 4.2 servings/day) versus lowest (0.8 servings/day) total dairy: total mortality HR 1.07 (95% CI 1.04 to 1.10); cardiovascular mortality 1.02 (0.95 to 1.08); cancer mortality 1.05 (0.99 to 1.11). Whole milk per additional 0.5 serving/day: total mortality 1.11 (1.09 to 1.14), cardiovascular mortality 1.09 (1.03 to 1.15). Cheese and yogurt were not associated with total or cause-specific mortality.

9. 独立研究

   Chen M, Sun Q, Giovannucci E, Mozaffarian D, Manson JE, Willett WC, et al. Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis BMC Medicine, 2014.

   doi:10.1186/s12916-014-0215-1PubMed 25420418

   資金と結果

   追跡期間

   up to 30 years; 3,984,203 person-years

   資金提供

   National Institutes of Health grants DK58845, P01 CA87969, P01 CA055075, R01 HL034594 and HL60712; NHLBI career development award R00HL098459. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

   結果

   15,156 incident type 2 diabetes cases in 3,984,203 person-years. Per serving/day: total dairy HR 0.99 (95% CI 0.98 to 1.01); yogurt 0.83 (0.75 to 0.92). Meta-analysis of 14 cohorts (35,863 cases): total dairy RR 0.98 (0.96 to 1.01) and yogurt 0.82 (0.70 to 0.96) per serving/day.

10. 独立研究

    Vimaleswaran KS, Zhou A, Cavadino A, Hyppönen E. Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals International Journal of Obesity, 2021.

    doi:10.1038/s41366-021-00841-2PubMed 34024907

    資金と結果

    資金提供

    British Heart Foundation (D-CarDia collaboration, PG/09/023); National Health and Medical Research Council, Australia (1123603); Rank Prize Funds Nutrition Committee Travel Award; Medical Research Council (MR/S024778/1).

    結果

    The T allele of the LCT variant rs4988235, which indexes higher milk intake, was associated with higher BMI and lower total, LDL and HDL cholesterol. Per T allele: coronary artery disease OR 0.86 (95% CI 0.75 to 0.99; CARDIoGRAM, 22,233 cases and 64,762 controls); type 2 diabetes OR 1.06 (0.97 to 1.16; DIAGRAM, 34,840 cases) and 0.89 (0.82 to 0.97; UK Biobank, 20,820 cases).

11. 独立研究

    Aune D, Navarro Rosenblatt DA, Chan DS, Vieira AR, Vieira R, Greenwood DC, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies American Journal of Clinical Nutrition, 2015.

    doi:10.3945/ajcn.113.067157PubMed 25527754

    資金と結果

    資金提供

    Supported by the World Cancer Research Fund (grant 2007/SP01) as part of the Continuous Update Project.

    結果

    Total prostate cancer, summary RR: total dairy products 1.07 (95% CI 1.02 to 1.12; 15 studies) per 400 g/day; total milk 1.03 (1.00 to 1.07; 14 studies) per 200 g/day; cheese 1.09 (1.02 to 1.18; 11 studies) per 50 g/day; dietary calcium 1.05 (1.02 to 1.09; 15 studies) per 400 mg/day. Dairy calcium, but not nondairy or supplemental calcium, was positively associated with total prostate cancer.

12. 企業資金

    Iuliano S, Poon S, Robbins J, Bui M, Wang X, De Groot L, et al. Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial BMJ, 2021.

    doi:10.1136/bmj.n2364PubMed 34670754

    資金と結果

    試験登録

    ACTRN12613000228785

    参加者

    7,195

    追跡期間

    2 years; mean 12.6 months per resident

    資金提供

    Grants from Dairy Australia (TP 701722), California Dairy Research Foundation, National Dairy Council, Aarhus University Hospital and Danish Dairy Research Foundation, Fonterra Co-operative Group Ltd, Dutch Dairy Association, Dairy Council of California, Dairy Farmers of Canada, Centre national interprofessionnel de l'economie laitiere, University of Melbourne, Austin Hospital Medical Research Foundation and Sir Edward Dunlop Medical Research Foundation. The funding groups played no role in design, execution, analyses, interpretation, writing or any other aspect of the study.

    現物支援

    Dairy foods provided in kind by Fonterra International (New Zealand).

    結果

    Cluster randomised by facility. Additional milk, yoghurt and cheese supplied 562 mg calcium and 12 g protein per day (dairy 2.0 to 3.5 servings/day). Fractures 121 (3.7%) intervention versus 203 (5.2%) control, HR 0.67 (95% CI 0.48 to 0.93); hip fractures, post hoc, 42 (1.3%) versus 93 (2.4%), HR 0.54 (0.35 to 0.83); falls 57% versus 62%, HR 0.89 (0.78 to 0.98); deaths 27% versus 28%, HR 1.01 (0.43 to 3.08). Numbers needed to treat: 52 for any fracture, 82 for hip fracture. Serum IGF-1 rose 5.9% with the intervention; between-group difference 7.9%.

13. コンセンサス

    Suchy FJ, Brannon PM, Carpenter TO, Fernandez JR, Gilsanz V, Gould JB, et al. National Institutes of Health Consensus Development Conference: lactose intolerance and health Annals of Internal Medicine, 2010.

    doi:10.7326/0003-4819-152-12-201006150-00248PubMed 20404261

    資金と結果

    資金提供

    Conference sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH Office of Medical Applications of Research; cosponsors NIDDK, NIH Division of Nutrition Research Coordination, National Institute on Aging and Office of Dietary Supplements; partners US Department of Agriculture and Health Resources and Services Administration. Informed by a systematic review from the Minnesota Evidence-based Practice Center under contract with AHRQ. The statement is an independent report of the panel.

    結果

    Adults and adolescents with diagnosed lactose malabsorption could ingest at least 12 g of lactose in a single dose (the lactose in 1 cup of milk) with no or minor symptoms; 50 g usually induced symptoms when taken without meals. Lactose does not necessarily affect the efficiency of calcium absorption, and persons with lactase non-persistence do not have substantial impairment in calcium absorption.

14. 規制当局

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 EFSA Journal, 2010.

    doi:10.2903/j.efsa.2010.1763

    資金と結果

    資金提供

    European Food Safety Authority, on request from the European Commission (Questions EFSA-Q-2008-1882, EFSA-Q-2008-3708). The evidence assessed was supplied by Member States and stakeholders.

    結果

    Thirteen of 14 human studies showed enhanced digestion of lactose in yoghurt in lactose maldigesters when live Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus were ingested in yoghurt; the panel concluded that a cause and effect relationship is established, with at least 10^8 CFU live starter microorganisms per gram. In one study about one fifth of the lactase activity contained in yoghurt reached the terminal ileum; in another the effect was destroyed by pasteurisation.